PURPOSE: Oral cancer causes considerable mortality across the globe, mainly due development of chemoresistance and lack of efficient chemotherapeutic agents. In the current study the anticancer potential of Acetylshikonin was examined against KB-R cisplatin-resistant oral cancer cells along with evaluation of in vitro and in vivo modes of action. METHODS: The proliferation rate of the oral cancer cells was checked by MTT assay. Autophagy was detected by electron microscopy. Apoptotic cell death was assessed by DAPI and annexin V/propidium iodide (PI) staining. Protein expression was determined by immunoblotting. Xenografted mice models were used for in vivo evaluation of Acetylshikonin. RESULTS: The results revealed that Acetylshikonin could significantly inhibit the proliferation of all the oral cancer cells with lower cytoxicity compared with the normal cells. The anticancer activity of Acetylshikonin against the KB-R cisplatin-resistant cells was found to be due to induction of autophagy and apoptosis. The Acetylshikonin prompted apoptosis and autophagy was also associated with alteration in the apoptosis and autophagy-related protein expression. Furthermore, it was observed that Acetylshikonin could inhibit the mTOR/PI3K/AKT signalling pathway in the cisplatin-resistant KB-R oral cancer cells. The effects of the Acetylshikonin were also examined in vivo in xenografted mice models and it was observed that Acetylshikonin inhibited the growth of xenografted tumors. CONCLUSIONS: These results suggest that Acetylshikonin considerably suppresses the growth of cisplatin-resistant oral cancer in vitro and in vivo and may prove beneficial in the treatment of drug-resistant oral cancer.
PURPOSE: Oral cancer causes considerable mortality across the globe, mainly due development of chemoresistance and lack of efficient chemotherapeutic agents. In the current study the anticancer potential of Acetylshikonin was examined against KB-R cisplatin-resistant oral cancer cells along with evaluation of in vitro and in vivo modes of action. METHODS: The proliferation rate of the oral cancer cells was checked by MTT assay. Autophagy was detected by electron microscopy. Apoptotic cell death was assessed by DAPI and annexin V/propidium iodide (PI) staining. Protein expression was determined by immunoblotting. Xenografted mice models were used for in vivo evaluation of Acetylshikonin. RESULTS: The results revealed that Acetylshikonin could significantly inhibit the proliferation of all the oral cancer cells with lower cytoxicity compared with the normal cells. The anticancer activity of Acetylshikonin against the KB-R cisplatin-resistant cells was found to be due to induction of autophagy and apoptosis. The Acetylshikonin prompted apoptosis and autophagy was also associated with alteration in the apoptosis and autophagy-related protein expression. Furthermore, it was observed that Acetylshikonin could inhibit the mTOR/PI3K/AKT signalling pathway in the cisplatin-resistant KB-R oral cancer cells. The effects of the Acetylshikonin were also examined in vivo in xenografted mice models and it was observed that Acetylshikonin inhibited the growth of xenografted tumors. CONCLUSIONS: These results suggest that Acetylshikonin considerably suppresses the growth of cisplatin-resistant oral cancer in vitro and in vivo and may prove beneficial in the treatment of drug-resistant oral cancer.